Project Summary-Sirica NIH R13 Conference Grant Primary hepatobiliary cancers, including hepatocellular carcinomas and intrahepatic cholangiocarcinomas, are a heterogeneous group of liver malignancies that present significant biological and clinical challenges largely related to their aggressiveness, typically advanced stage at the time of diagnosis, high recurrence rates after surgical resection, and refractoriness to current medical therapies. This first of its kind single topic conference, which is being sponsored and funded in part by the American Association for the Study of Liver Diseases and The Cholangiocarcinoma Foundation, is uniquely focused on disseminating cutting edge basic and translational research findings, which include sharing significant unpublished work, aimed at providing new mechanistic insights into the cellular and molecular pathogenesis of hepatobiliary cancers and advancing present and emerging translational approaches towards identifying and personalizing more effective targeted therapies, as well as devising needed prevention strategies to reverse the unfavorable trends associated with these devastating liver cancers. Key topic areas that will be covered include hepatobiliary cancer signaling pathways, stemness, microenvironment, microRNA dysregulation, epigenetic modifications and therapeutics, genomic profiling, molecular and immunotherapeutic targeting, changing etiology, and future challenges for therapy and prevention. The conference is designed to balance presentations by preeminent senior leaders with those from accomplished early career investigators whose current research is having a promising impact on the field. Presentations by liver cancer patient advocate organizations and from industry will also be represented at the conference. Importantly, the conference will promote scientific community, productive discussions, and diversity allowing for meaningful representation by women and minorities as session chairs, invited speakers, young investigator poster presenters, and attendees. The Young Investigator Poster Session that is included as part of the scientific program is also indicative of the conference's goal to provide a mentoring environment that fosters the career development of the next generation of liver cancer researchers. Another desired aim is to generate a co-authored review articles for peer-review publication in high impact journals that discuss timely new and future research directions and therapeutic strategies advanced at the conference.